1. Sea Anemone….To Treat or not to Treat: That is the Question?
CT Surgery/Cardiology Conference
Shadwan Alsafwah, MD
Cardiology Fellow
University of Tennessee at Memphis

2. Case
53 YO M with OSA was referred for OP routine TTE for evaluation of pulmonary HTN.
PMH:
OSA
HTN
Hyperlipedemia
Asthma
Colon Polyposis
BPH
LUE weakness and tremor since 6 months

3. Case…… Meds: Albuterol Lisinopril Simvastatin Terazosin PSH:
Hernia repair
SH:
Smoker 1ppd X 30 y
No ETOH, illicit drugs
Allergies:
Sulfa
Metronidazol
Codien

4. Case… Physical exam: Vitals: 154/77, 65, 16, 97.7
Neck: No JVD, No Carotid Bruit.
Chest: CTAB
CVS: RRR, normal S1, S2, no extra sounds
Abdomen: Soft, NT, ND, NABS
Ext: No E/C/C
Neuro: Normal except for Motor 4/5 in LUE

5. 2 D Echo EF: normal estimated 75%
Borderline mild pulmonary hypertension (peak PA pressure mm Hg.
Mild –moderate LVH
Fimbria-like structure on the aortic valve, most likely papillary fibromatous tumor. Less likely to be vegitation or Lambl’s Excrescence.
TEE recommended

6. TEE
Fimbriae-like structure on the right coronary cusp of the aortic valve C/W Papilary fibroelastoma (not likely to be a lambl’s excrescence, or vegetations)
Otherwise normal aorta
Normal LV function, EF 75%

7. Better Be Prepared for Questions like:
What does this “structure” mean?
What caused it?
What should we do about it?

8. Outline Nomenclature Historical Reference Incidence Natural History
Etiologies
Anatomy: - Gross
- Micro
Clinical Manifestations
Diagnostic Modalities
Differential Diagnosis
Treatment
Prognosis
Summary

9. Nomenclature Fibroma Cardiac papiloma Valvar papiloma Myxofibroma
Fibroelastic hamartoma
Endocardiac papillary fibroma
Giant Lambl’s excrescences
Cardiac Papillary Fibroelastoma (CPF)

10. Historical Reference
The first cardiac tumor ever described was a left atrial myxoma described in 1845 by King TW :
“ On simple vascular growth in the left auricle
of the heart” Lancet 1845;2:
Yater in 1931 was the first to describe the valvular tumors
Cheitlin et al in 1975 used the term “papillary fibroelastoma” for the first time.
Lichtenstein et al in 1979 were the first to report a CPF found incidentally during VSD repair.
Flotte et al diagnosed this tumor on Echo 1980

11. Incidence
Historically was the third most common benign primary cardiac tumor after Myxomas, Lipomas
More recent series has placed it as the second most common benign primary tumor of the adult heart.
The most common primary tumor of the cardiac valves (3/4th)
Has an estimated incidence of %-0.33% in autopsy series, and an estimated echocardiography incidence of 0.019%

12. Incidence…
90% arise from valvular tissue, most commonly aortic (44%) or mitral valves (35%). They may arise from papilary muscles and chordae tendineae, but rarely from the mural endocardium
Most commonly they arise from the mid portion of the valve. They project into the arterial lumen of semilunar valves and the atrial surface of AV valves
Reported from neonates to 92 years, but in general rarely seen below age 20, with mean age of 60 years, and 29% were 70 years of age or older.
Males = Females

13. Benign Primary Cardiac Tumors

14. Natural History
Significant percentage of patients have concomittent valvular disease, suggesting that prior endocardial damage predisposes to papiloma formation
Generaly, Small in size:
- 99% <20 mm in largest dimension (mean 9 mm)
- Range 2-70 mm in size
More than 90% are solitary
Slow- grwoing tumor

15. Etiologies Remains under discussion, possible etiologies:
Truly neoplastic
Viral
Iatrogenic:
1. Post cardiac surgery
2. Post radiation therapy
Other possible etiologies

16. (?) Viral Small study at Hospital Cardiologique, Chulille, France.
4 patients with valvular CPF:
2 with prior neuro embolic events
2 without prior embolic events
CPFs were surgically removed, and all samples were histologically confirmed
Specific immunohistochemical (IHC) studies were conducted on all samples
Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41

17. (?) Viral
The first 2 patients: there was good correlation between the neuro events and the presence of thrombus aggregated on the injured superficial endothelial layer.
The other 2 patients: no endothelial damage or thrombus were found.
IHC studies showed:
-A centrifugal mesenchymal cellular migration arising from the
central layer to the superficial layer with differentiation steps.
-The presence of dendritic cells and remnants of CMV in the
intermediate layer.
Is CPF a chronic form of viral endocarditis.
Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41

18. (?) Iatrogenic
A study at Mayo clinic and Armed forces Institute of Pathology in washington, DC found 12 iatrogenic CPF cases (6 post CT surgery, 6 post thoracic irradiation) between :
1. Common: It represented 18% of all surgically
excised CPF during that period!
2. Timing: mean interval was 18 years (range 9-31 years)
3. Multiple: about 58% were multiple!
4. Location: found in the chamber closest to the procedure, or
within the radiation field
5. Atypical: often involve nonvalvular endocardial surfaces
Kurup AN, et al. Hum Pathol 2002;33(12):1165-9

19. (?) Other Possible Etiologies
Mechanical damage to the endothelium
Organizing thrombi
Hamartomous origin or congenital etiologies in neonates/infants (very rare)

20. Gross Anatomy Resemble a sea anemone:
Friable, white to tan multiple branching
and nonbranching fingerlike fronds emanating from a stalked central core

21. Microscopically Each frond is avascular and consists of a
collagenous core surrounded
by elastic fibers and loose
mucopolysaccharide matrix
with rare smooth muscle cells
And covered by a single layer
of endocardial endothelial cells

22. Clinical Manifestations
More than 60% asymptomatic, found incidentally
Do not generally cause valvular dysfunction
But, sometimes can cause:
1. Embolic Phenomena leading to TIAs and CVAs:
- Can be as high as 25% over 3 years, and 6% in
asymptomatic incidental CPF
-Results from fragmentation of the papillary spikelets
of the tumor or from thrombi formed by platelets
and fibrin adhering to the uneven surface of CPF
-A/C of ? effect (3 cases with recurrent strokes while on A/C)

23. Other Clinical Manifestations..
- The tumor mobility was the only independent predictor of CPF related death or nonfatal embolization
2. Angina Pectoris, sometimes AMI if it involves the coronary ostium
3. Outflow tract obstruction, presyncope or
syncope
4. Sudden death
5. It can get infected! (SBE prophylaxis?)

28. Diagnosis
Should be suspected in young patients with no evidence of cerebrovascular disease who present with an embolic cerebral stroke, especially in the presence of NSR
Before 1977, they were diagnosed exclusively at postmortem examination
Up to 1991 only 132 cases were reported in the literature
Now, it is generally an incidental finding by routine TTE echocardiography (sensitivity 62%)
Best seen by TEE (sensitivity 77%)
Either TTE, TEE sensitivity is up to 90% if size >20 mm

29. Typical Echocardiographic Features
Round, oval, irregular in appearance
Well-demarcated borders
Homogenous texture
Nearly half have small mobile stalk
TEE with its high resolution, may distinguish the collagen center of the tumor from other cardiac structures, due to its shining echo appearance
It can rarely become calcified

35. Cardiac MRI and Ultrafast CT
CPF are usually not seen at MRI or CT, due to their size (very small in general) and location (moving valves)
Detects only exceptionally large CPF, or
atypical CPF (away from valves)
MRI is generally preferred to CT as it reflects the chemical microenvironment within the tumor (better soft-tissue characterization), offering clues to the type of tumor
Will have more role in near future with new emerging advances in technology?

43. Differential Diagnosis
Lambl’s excrescences
Myxoma
Bacterial vegetations
Organizing marantic (thrombotic) endocarditis

44. CPF Vs Lambl’s Excrescences
Location: Valve surface
Rarely multiple
Gross: Small, branching
Micro: abundant subendothelial myxoid ground substance
Etiology: Multiple theories
Very rare
At sites of valve closure
> 90% multiple
Smaller, non branching
Less abundant subendothelial myxoid ground substance
Endothelial damage, followed by thrombosis
and organization.
Common: more than 70% of adults

45. Treatment
Controversial, due to the absence of randomized controlled data available
Long-term oral A/C +/- Antiplatelet therapy could be offered to symptomatic patients who are not surgical candidates, but its efficacy in preventing embolic events is unclear.
SBE prophylaxis (?)

46. Sun JP, et al. Circualtion 2001;103:2687

47. 162 patient found to have pathologically confirmed CPFs:
Study Design
Retrospective + Prospective 16-year study ( ) using echo (total echos) and pathology data base at CCF.
162 patient found to have pathologically confirmed CPFs:
- in 141 an Echo (126 TTE, 107 TEE) was performed
-of those 93 CPFs identified: - 26 identified pre-surgery
(prospectively)
- 67 identified post-surgery
(retrospectively)
An additional 45 patients with presumed CPF identified by echo database were followed for symptoms attributable to CPF.
Sun JP, et al. Circulation 2001;103:2687

48. Sun, JP, et al. Circulation 2001;103:2687 Results
23/26 patients in the Prospective group developed symptoms.
5/45 patients in the presumed group developed symptoms.
Stalks with mobility were present in almost all the symptomatic ones
Sun JP, et al. Circulation 2001;103:2687

49. Treatment of Right-sided CPF
Right-sided CPF are less risky, surgery is not completely agreed upon, but generally surgery is indicated if:
1. Symptomatic
2. Large mobile tumors
3. Presence of PFO with a sizable right to left
shunt

50. Treatment of Left-sided CPF
Somewhat less controversial:
In general: it should be removed, especially:
1. Symptomatic
2. CPF≥ 1 cm, especially if mobile
3. Young patients with low risk of surgery and
high risk for embolization
4. Patients with other cardiovascular disease.
Asymptomatic patients with small, left-sided nonmobile CPF can be followed-up closely with periodic clinical evaluations and echo, and receive surgical intervention whenever symptoms develop or the tumor becomes mobile

51. Prognosis
Surgical removal is usually curative after complete resection, never reported to recur in the same location
CPF can recur in another location
More than 90% can be resected using conservative valve- sparing approaches
Incidental CPF found on the aortic or mitral valves during other surgery should be removed.
Long-term f/u is recommended

52. Back to Our Question:
Sea anemone: To treat or not to treat, that is the question?
The best advise is:
Individualize, look at each case separately

53. Consider in your Decision..
The Patient: -Age : the younger the pt the higher the
cumulative risk of embolization
-Other co-morbidities…
Symptomatic CPF or not
If symtomatic: what strength of association of the tumor with symptoms
CPF Size (≥ or < 1 cm)
CPF Location (L sided or R sided, valvular or nonvalvular…)
CPF mobility (i.e. presence of stalk or not)

54. Now Back to Our Patient He is 53 Y.O.
No major co morbidities/contraindications for surgery.
His CPF is on the Aortic valve
< 1 CM
nonmobile
The major question is whether the LUE weakness represent an ischemic event or not.

55. Summary
CPF is increasingly recognized with the widespread use of TTE, TEE, and with new imaging modalities
It should be differentiated from other valvular pathologies especially Lambl’s excrescences.
It can be symptomatic, mainly manifesting as embolic disease
Controverseries still ongoing about the pathogenesis and treatment of incidental CPF
More studies are needed to clarify its pathogenesis, and treatment.

56. Thank You